The invention relates to a generally practicable method of performing cyclization reactions with the yielding of a submolecule, which take place only at relatively high temperatures above those which can be achieved with conventional solvents.
The method is especially suitable for those cyclization reactions in which an alcohol is split off from an ester group of the starting substance.
Such reactions have hitherto been conducted but incompletely, because at the high temperature at which the splitting off of the alcohol group and the cyclization reactions take place numerous secondary and competing reactions diminish the yeild and contaminate the desired product. It is known, for example, that in the cyclization of 2-pyridylaminomethylenemalonic acid esters with the removal of alcohol, 1,8-naphthyridine derivatives are formed. According to R. Lappin, J. Am. Chem. Soc. 70 (1948), 3348, however, 7-methyl-4-hydroxy-3-carbethoxynaphthyridine 1,8 is obtained in a good yield only if the methylpyridylaminomethylenemalonic acid diethyl ester is fed to a refluxing solution of diphenyl ether at about 260.degree. C and the reaction solution is chilled as quickly as possible after a reaction time of 10 minutes. In this process small amounts around approximately 0.1 mole produce good yields, whereas Lappin obtains "much smaller yields without exception" from larger batches. Our own experiments resulted, despite rapid chilling, in a reduction of the yield to 45 to 55% of the theory as soon as the input was increased above about 20 grams.